1. Implications of the TRANSFER AMI Trial for
Clinical Practice
Tim Henry, MD
Director of Research
Minneapolis Heart Institute
Foundation

2. Clinical Practice in 2010:
Standard of Care?
• PCI centers should do PCI (in a timely
manner <90 min)
• Short Distance Transfer Pts should
have PCI (in a timely manner <120?)
• Long Distance transfer or Pts with
expected delay remains an area of
controversy!!

3. Raising the Bar on Reperfusion
Speed for STEMI
• Door-to-balloon
(D2B) time <90 min
(Class I-A)
• First Medical
contact-to-balloon <
90min (Class I-B)
• ACC/AHA 2004 STEMI
Guidelines JACC 44:671

4. Primary PCI: Access
• 42.0% PCI hospital is closest facility
• 79.0% within 60 minute prehospital time
Nallamothu et al. Circulation 2006;113:1189

5. STEMI – Door to Balloon and Door to Needle Times:
Cumulative 12 Month Data
100%
81%
80%
60% 57%
40%
High performing institutions are engaged in QI Monitoring
18%
20%
0%
DTB <= 90 min - DTB <= 90 min - DTN <= 30 min - All
Non-Transfer In Transfer In
ACTION Registry-GWTG DATA: January 1 – December 31, 2008
DTB = 1st Door to Balloon for Primary PCI
DTN = Door to Needle for Lytics

6. What is the Optimal Reperfusion
Strategy for STEMI Patients with
expected delays?

7. Real Life!
• 70 year old Lawyer presents to ED
120 miles from a PCI center with
acute onset of 9/10 chest pain at
09:15 pm called 911.
• Arrived at the community ED at 9:36
EKG obtained at 9:43

9. Options for Patients with
Prolonged Transfer Times
1. Full dose fibrinolytic with elective transfer or
for rescue
2. Full dose fibrinolytic with routine transfer
and rescue as needed
3. Facilitated PCI
4. Primary PCI (no matter how long it takes)
5. All of the above: Depending on the time of
day and which cardiologist is on call!

10. PCI is better than LYSIS!

11. Primary PCI vs Lysis for STEMI –
Meta-analysis of 23 trials
Short Term Events P<0.0001
16
14
14
12 P=0.0003
10 P<0.0001 8
7
PTCA
8 7
p=0.0004 Thrombolytic
6 5
P<0.0001
4 3
1 2
2 1
0.05
0
Death Re MI Total ICH Death +
CVA Re-MI +
CVA
Keeley, Lancet Jan 2003

12. Cumulative Mortality During the First Year
Stenestrand, U. et al. JAMA 2006;296:1749-1756.

13. Transfer for PCI is better
than LYSIS!
(In a timely manner)

15. Relative Risks of Transfer for Primary
PCI vs Fibrinolysis

16. Rescue PCI
is better than
LYSIS!

17. REACT:
6 month Primary composite
(Death, MI, CVA, or severe heart failure)
•The primary composite
endpoint of death, MI, CVA or
severe heart failure at 6 months
35 p<0.001 p=0.002
31.0 was significantly lower in the
29.8 rescue PCI group compared
30
with either the repeat
25 thrombolysis group or the
conservative management
20 group
15.3
%
15
10
5
0
Repeat Rescue PCI Conservative
Thrombolysis Management
Presented at AHA 2004

18. Immediate PCI
is better than
LYSIS +/- Delayed PCI!

19. SIAM 3
Event Free Survival
(Death, Reinfarction, Intervention, Ischemia)

20. PCI
is better than
Facilitated PCI
????

21. Facilitated PCI
Dauerman and Sobel. JACC 2003

22. Limitations of ASSENT-4
• Full dose Lytic: Focus on bleeding not patency
• Inadequate antiplatelet (No IIb/IIIa / delayed
clopidogrel)
• Inadequate antithrombin (bolus only)
• Lower patency than expected
• 15% of deaths were CVA
• 45% in PCI hospital
• < 5% US
• Limited transfer delays (excluded long delays)

23. FINESSE: Study Design
Acute ST-elevation MI (or new LBBB) within 6h pain onset
Presenting at Hub or Spoke with estimated time to PCI between 1 and 4 hours
Randomize 1:1:1
N=3000 *Only 5U if ≥ 75
Placebo Placebo Reteplase (5U+5U)*
Placebo Abciximab Abciximab
Transfer To Cath Lab
ASA, unfractionated heparin 40U/kg (max 3000 U)
or enoxaparin (0.5 mg/kg IV + 0.3 mg/kg SC) – substudy only
Abciximab Placebo Placebo
Primary PCI with Abciximab Infusion (12 h)
Primary endpoint at 90 days: All- cause mortality, resuscitated VF
occurring > 48h, cardiogenic shock, or readmission/ED visit for CHF

24. TIMI Flow in IRA Pre-PCI
% Subjects with TIMI 2/3 (Patency) Pre-PCI
120%
p<0.0001
100%
80% p<0.0001
61%
Percentage
60% TIMI 2
25%
40% 25% 26%
20% 12% 11% 36% TIMI 3
13% 15%
0%
Primary PCI (in lab Abciximab Facilitated Reteplase/Abciximab
Abciximab) (n=790) PCI (n=809) Facilitated PCI (n=815)
Ave Time from First Abciximab Bolus
to Angiogram In Facilitated Groups: 74min 76min
Modified ITT Population with Index PCI: ITT, PCI and any dose of study drug (active or placebo); Investigator assessment

25. Primary Endpoint
10.7%
10.5%
9.8%

26. FINESSE
• Best trial available
• Slow enrollment, therefore underpowered
• 40% spoke hospitals with D-B 155 min
• Increase bleeding (are all regimens =?)
• Signals in Ant MI, High Risk, < 3 hrs

28. Pharmacoinvasive
(Facilitated) PCI
is better than Lytic +
Rescue PCI

29. CARESS: Treatment summary
ASA 300-500 mg iv
ASA 300-500 mg iv
2 xx5 U bolus (30’) Reteplase
2 5 U bolus (30’) Reteplase
UFH (40 U/kg (max 3000); 7 U/kg/h)
UFH (40 U/kg (max 3000); 7 U/kg/h)
Abciximab 0.25 mg/kg bolus
Abciximab 0.25 mg/kg bolus
0.125 µg/kg/min xx12 h
0.125 µg/kg/min 12 h
FACILITATED PCI MEDICAL TREATMENT/ RESCUE
40 U/kg Heparin Bolus (max. 3,000
40 U/kg Heparin Bolus (max. 3,000 40 U/kg Heparin Bolus (max. 3,000
40 U/kg Heparin Bolus (max. 3,000
U) + 7 U/Kg/h during transfer
U) + 7 U/Kg/h during transfer U) + 7 U/Kg/h for 24 hours
U) + 7 U/Kg/h for 24 hours
PCI ACT adjusted to 200-250” and
PCI ACT adjusted to 200-250” and In case of Rescue PCI ACT
In case of Rescue PCI ACT
heparin stopped after procedure
heparin stopped after procedure adjusted to 200-250” and heparin
adjusted to 200-250” and heparin
stopped after procedure
stopped after procedure
Clopidogrel Started in the Cath Lab and Maintained for 1-12
Clopidogrel Started in the Cath Lab and Maintained for 1-12
months only after Stenting up to Nov 2005 (514 Pts, 82%)
months only after Stenting up to Nov 2005 (514 Pts, 82%)

30. Primary Outcome at 30 days
Death, re-MI, refractory ischaemia
11.1%
OR 0.34 (95%CI 0.17-0.68) P=0.001
4.1%

31. ‘High Risk’ ST Elevation MI within 12 hours of symptom onset
TNK + ASA + Heparin / Enoxaparin + Clopidogrel
Community
Hospital “Pharmacoinvasive “Standard Treatment”
Strategy”
Emergency Urgent Transfer to PCI Centre
Assess chest pain, ST↑ resolution
Department at 60-90 minutes after randomization
Failed Reperfusion* Successful Reperfusion
Cath / PCI within 6 Cath and Rescue Elective Cath
hrs regardless of PCI ± GP IIb/IIIa ± PCI
PCI Centre reperfusion status Inhibitor > 24 hrs later
Cath Lab
Repatriation of stable patients within 24 hrs of PCI
ST segment resolution < 50% & persistent chest pain, or hemodynamic instability
Randomization stratified by age (≤75 vs. > 75) and by enrolling site

32. Primary Endpoint: 30-Day Death, re-
MI, CHF, Severe Recurrent Ischemia,
18
% of Patients
Shock 16.6
16
14
OR=0.537 (0.368, 0.783); p=0.0013
12
10.6
10
8
6
4 Standard (n=496)
2 Pharmacoinvasive (n=508)
0
0 5 10 15 20 25 30
Days from Randomization
n=496 422 415 415 414 414 412
n=508 468 466 463 461 460 457

33. Problems with a Rescue Strategy
• How do you decide when to go?
• Who decides when to go?
• Guaranteed delays!!!
• And cath lab unhappiness
• CARESS and
TRANSFER AMI !!!!!

34. Problems with PCI no matter
how long it takes!
• Time may be less critical with PCI but
TIME STILL MATTERS!
• Delays still occur especially with
Transfer Pts (<15% treated <2hours)
• When your mother (or your lawyer Pt)
has a large Anterior STEMI do you
want them waiting 3 hours for
Reperfusion?

35. Options for Patients with
Prolonged Transfer Times
• Full dose fibrinolytic with elective transfer or
for rescue
• Full dose fibrinolytic with routine transfer and
rescue as needed
• Primary PCI (no matter how long it takes)
• Pharmacoinvasive PCI
• All of the above: Depending on the time of
day and which cardiologist is on call!

38. What conclusions can we make!
• PCI centers should do PCI (in a timely
manner <90 min)
• Short Distance Transfer Pts should have PCI
(in a timely manner <120?)
• Pharmcoinvasive PCI is an excellent choice
for Pts with expected delay!!
• The ideal regimen and timing of PCI remain
unclear!

40. Facilitated PCI
• ACC/AHA guidelines include facilitated
PCI as a IIa recommendation
• Reduced dose fibrinolytic followed by
PCI results in earlier reperfusion
• Pharmacoinvasive PCI maybe a better
reperfusion strategy to primary PCI
when transfer delays are expected

41. Never tested
≠
No Benefit

42. Time from Symptom Onset to Treatment
Predicts 1-year Mortality after Primary PCI
n=1791
The relative risk of 1-year mortality increases by
7.5% for each 30-minute delay
De Luca et al, Circulation 2004;109:1223-1225

43. Door-to-Balloon Time< 90 Minutes
by Transfer Status
41%
45
Non-transfer
Percent of Patients
40
33.1%
35
30
25
20
15
Transfer
10
5 3.9% 5.4%
0
1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004
R Brindis Year of Discharge Nallamothu et al
ACC 2005 Circ 111: 761:2005

44. There Still is a Role for
Facilitated PCI!
We just need to change the NAME!
• Pharmacoinvasive strategy
• FAST PCI
• ROUTINE RESCUE PCI

45. “Humanity’s greatest advances
are not in its discoveries – but in
how those discoveries are
applied ...” Bill Gates, June 7, 2007
Harvard Commencement Address

46. Limitations of Keeley Meta-analysis
• 17 trials with tremendous variation:
– 9: IIb/IIIa only
– 6: lytic only
– 2: ½ dose + IIb/IIIa
• No trials in Pts with transfer delay
• 50% of Lytic data from Assent 4
• Relatively low risk pts in PCI hospitals or with
short transfer distances

47. FINESSE Enrollment (2002-2006):
Projection vs Actual
N=2452
Enrollment
Terminated
Dec 30, 2006

48. ST Segment Resolution (>70%)
at 60-90 Min: Core Lab
% Evaluable Subjects with ST Segment Resolution
100%
p=0.003 p=0.010 p=NS
80% p=0.013 p=0.011
64%
Percentage
57%
60% 51%
44%
36%
40% 31% 33%
23% 24%
20%
0%
All (n=745) Prior to Balloon After Balloon
Inflation (n=525) Inflation (n=154)
Primary PCI with in lab Abciximab (n=242)
Abciximab Facililated PCI (n=257)
Reteplase/Abciximab Facilitated PCI (n=246)
*Half of subjects randomly selected for Core Lab over-read

49. Major Secondary Endpoints
All Cause Mortality Complications of MI
8.9%
7.5%
5.5% 7.4%
5.2%
4.5%

50. Michael Simons, MD, Nathaniel W. Niles, MD
Timothy D. Henry, MD,
David M. Larson, MD Holger Thiele, MD
Gerhard Schuler, MD
AMICO: Alliance for
Myocardial Infarction
Care Optimization
Ali. E. Denktas, MD, Haris Athar, MD, Stefano Sdringola, MD,
H. Vernon Anderson, MD, Richard W. Smalling, MD, PhD
Chul Ahn, PhD
Raymond G. McKay, MD

51. AMICO Registry
30-Day Outcomes
FAST-PCI PPCI
p = <0.0001
10.0%
8.90%
9.0% p = 0.002
8.0%
7.0% 6.30%
6.0%
5%
5.0%
4.0% 3.60% p = NS p = 0.0006
3.0%
1.90%
2.0% 1.40%
1.10% 0.80%
1.0%
0.0%
Death Stroke Re-MI Any Event

52. CAPITAL AMI Trial
Primary Composite 30-Day 30-Day Recurrent
Reinfarction Unstable Ischemia
Endpoint at 30 days
p=0.034
25% 20% 17 .9 %
21.4% 15%
11.9 %
10%
20% 4 .7 %
7.0 %
5%
0%
15% TNK TNK TNK TNK
+PCI +PCI
%
10% 9.3% • Composite event rate remained
lower in the TNK+PCI arm at 30
days, again driven by reductions in
5% reinfarction and recurrent unstable
ischemia, with no difference in
0% mortality (2.3% vs. 3.6%).
• Length of hospital stay shorter in
TNK TNK+PCI
the TNK+PCI arm (5 vs. 6 days,
p=0.009).
Presented at ACC Scientific Sessions 2004

53. What Happened in Real Life
• MHI Level 1 MI protocol activated
• ASA, Clopidogrel 600mg, IV
heparin, IV metoprolol
• ½ dose lytic at 10:03 (door to
needle time 27 minutes)
• Repeat EKG while waiting for
helicopter

54. The Number of Randomized Trials
in Patients with Prolonged
Transfer Times
0

55. All Facilitated PCI
regimens are not
created = !!!!